Handheld physiological sensor

ABSTRACT

A handheld device measures all vital signs and some hemodynamic parameters from the human body and transmits measured information wirelessly to a web-based system, where the information can be analyzed by a clinician to help diagnose a patient. The system utilizes our discovery that bio-impedance signals used to determine vital signs and hemodynamic parameters can be measured over a conduction pathway extending from the patient&#39;s wrist to a location on their thoracic cavity, e.g. their chest or navel. The device&#39;s form factor can include re-usable electrode materials to reduce costs. Measurements made by the handheld device, which use the belly button as a ‘fiducial’ marker, facilitate consistent, daily measurements, thereby reducing positioning errors that reduce accuracy of standard impedance measurements. In this and other ways, the handheld device provides an effective tool for characterizing patients with chronic diseases, such as heart failure, renal disease, and hypertension.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.14/988,688, filed Jan. 5, 2016, now U.S. Pat. No. 10,206,600, which isincorporated herein in its entirety by reference.

BACKGROUND AND FIELD OF THE INVENTION 1. Field of the Invention

The invention relates to sensors that measure physiological signals frompatients, and the use of such sensors.

2. General Background

Physiological sensors, such as vital sign monitors, typically measuresignals from a patient to determine time-varying waveforms, e.g.thoracic bio-impedance (TBI), bio-reactance (BR), and electrocardiogram(ECG) waveforms, with electrodes that attach to the patient's skin.These waveforms can be processed/analyzed to extract other medicallyrelevant parameters such as heart rate (HR) and heart rate variability(HRV), respiration rate (RR), stroke volume (SV), cardiac output (CO),and information relating to thoracic fluids, e.g. thoracic fluid index(TFC) and general body fluids (FLUIDS). Certain physiological conditionscan be identified from these parameters using one-time measurements;other conditions require observation of time-dependent trends in theparameters in order to identify the underlying condition. In all cases,it is important to measure the parameters with high repeatability andaccuracy.

Some conditions require various physiological parameters to be measuredover a relatively short period of time in order to identify thecondition. For example, Holter monitors can characterize various typesof cardiac arrhythmias by measuring HR, HRV, and ECG waveforms overperiods ranging from a day to a few weeks. On the other hand, chronicdiseases such as congestive heart failure (CHF) and end-stage renaldisease (ESRD) typically require periodic measurements of FLUIDS andweight throughout the patient's life in order to identify the condition.Not surprisingly, patient compliance with measurement routines typicallydecreases as the measurement period increases. This is particularly truewhen measurements are made outside of a conventional medical facility,e.g., at the patient's home or in a residential facility such as anursing home.

Furthermore, the measured values of some physiological parameters willvary with the location at which the parameters are measured, while thoseassociated with other physiological parameters are relativelyindependent of the location at which the parameters are measured. Forexample, parameters such as HR, which depends on the time-dependentvariation of R-R intervals associated with QRS complexes in ECGwaveforms, are relatively insensitive to sensor positioning. Likewise,pulse oximetry (SpO2) and pulse rate (PR), as measured fromphotoplethysmogram (PPG) waveforms with a pulse oximeter, show littlevariance with measurement location.

On the other hand, measurements that depend on amplitude-dependentfeatures in waveforms, such as TFC or FLUIDS, will be strongly dependenton the measurement location, e.g. the positioning of electrodes. In thecase of TFC, for example, the measured value depends strongly on thesensed impedance between a set of electrodes. And this, in turn, willvary with the electrodes' placement. TFC deviation in the day-to-dayplacement of the electrodes can result in measurement errors. This, inturn, can lead to misinformation (particularly when trends of themeasured parameters are to be extracted), thereby nullifying the valueof such measurements and thus negatively impacting treatment.

Like TFC, measured values of blood pressure (BP), such as systolic(SYS), diastolic (DIA), and pulse (PP) pressures are typically sensitiveto the location at which the parameter is measured. For example, bloodpressure measured at the brachial artery with a sphygmomanometer (i.e. amanual blood pressure cuff) or with an oscillometric device (i.e. anautomated blood pressure cuff measuring oscillometric waveforms) willtypically be different from that measured at other locations on thebody, such as the wrist, thigh, finger, or even the opposite arm. Meanarterial pressure (MAP) is less sensitive to position, as it isrelatively constant throughout the body. Body (e.g. skin) temperature issimilarly dependent on the location at which it is measured, althoughcore temperature (TEMP), as measured from the ear or mouth, isrelatively consistent from one location to another.

3. Sensors, Devices, and Relevant Physiology

Disposable electrodes that measure ECG and TBI waveforms are typicallyworn on the patient's chest or legs and include: i) a conductivehydrogel that contacts the patient's skin; ii) a Ag/AgCl-coated eyeletthat contacts the hydrogel; iii) a conductive metal post that connectsto a lead wire or cable extending from the sensing device; and iv) anadhesive backing that adheres the electrode to the patient.Unfortunately, during a measurement, the lead wires can pull on theelectrodes if the device is moved relative to the patient's body, or ifthe patient ambulates and snags the lead wires on surrounding objects.Such pulling can be uncomfortable or even painful, particularly wherethe electrodes are attached to hirsute parts of the body, and this caninhibit patient compliance with long-term monitoring. Moreover, theseactions can degrade or even completely eliminate adhesion of theelectrodes to the patient's skin, and in some cases completely destroythe electrodes' ability to sense the physiological signals at variouselectrode locations.

Some devices that measure ECG and TBI waveforms are worn entirely on thepatient's body. These devices have been developed to feature simple,patch-type systems that include both analog and digital electronicsconnected directly to underlying electrodes. Such devices, like theHolter monitors described above, are typically prescribed for relativelyshort periods of time, e.g. for a period of time ranging from a day toseveral weeks. They are typically wireless and include features such asBluetooth® transceivers to transmit information over a short distance toa second device, which then transmits the information via a cellularradio to a web-based system.

SpO2 values are almost always measured at the patient's fingers,earlobes, or, in some cases, the forehead. In these cases, patients wearan optical sensor to measure PPG waveforms, which are then processed toyield SpO2 and PR values. TEMP is typically measured with a thermometerinserted into the patient's mouth, or with an optical sensor featuringan infrared-sensitive photodiode pointed into the patient's ear.

Assessing FLUIDS, TFC, weight, and hydration status is important in thediagnosis and management of many diseases. For example, ESRD occurs whena patient's kidneys are no longer able to work at a level needed forday-to-day life. The disease is most commonly caused by diabetes andhigh blood pressure, and is characterized by swings in SYS and DIA alongwith a gradual increase in FLUIDS throughout the body. Patientssuffering from ESRD typically require hemodialysis or ultrafiltration toremove excess fluids. Thus, accurate measurement of this parameterand/or TFC to characterize ESRD can eliminate the need for empiricalclinical estimations that often lead to over-removal or under-removal offluids during dialysis, thereby preventing hemodynamic instability andhypotensive episodes (Anand et al., “Monitoring Changes in Fluid StatusWith a Wireless Multisensor Monitor: Results From the Fluid RemovalDuring Adherent Renal Monitoring (FARM) Study,” Congest Heart Fail.2012; 18:32-36). A similar situation exists with respect to CHF, whichis a complicated disease typically monitored using a “constellation” ofphysiological factors, e.g., fluid status (e.g. FLUIDS, TFC), vitalsigns (i.e., HR, RR, TEMP, SYS, DIA, and SpO2), and hemodynamicparameters (e.g. CO, SV). Accurate measurement of these parameters canaid in managing patients, particularly in connection with dispensingdiuretic medications, and thus reduce expensive hospital readmissions(Packer et al., “Utility of Impedance Cardiography for theIdentification of Short-Term Risk of Clinical Decompensation in StablePatients With Chronic Heart Failure,” J Am Coll Cardiol 2006;47:2245-52).

CHF is a particular type of heart failure (HF), which is a chronicdisease driven by complex pathophysiology. In general terms, HF occurswhen SV and CO are insufficient to adequately perfuse the kidneys andlungs. Causes of this disease are well known and typically includecoronary heart disease, diabetes, hypertension, obesity, smoking, andvalvular heart disease. In systolic HF, ejection fraction (EF) can bediminished (<50%), whereas in diastolic HF this parameter is typicallynormal (>65%). The common signifying characteristic of both forms ofheart failure is time-dependent elevation of the pressure within theleft atrium at the end of its contraction cycle, or left ventricularend-diastolic pressure (LVEDP). Chronic elevation of LVEDP causestransudation of fluid from the pulmonary veins into the lungs, resultingin shortness of breath (dyspnea), rapid breathing (tachypnea), andfatigue with exertion due to the mismatch of oxygen delivery and oxygendemand throughout the body. Thus, early compensatory mechanisms for HFthat can be detected fairly easily include increased RR and HR.

As CO is compromised, the kidneys respond with decreased filtrationcapability, thus driving retention of sodium and water and leading to anincrease in intravascular volume. As the LVEDP rises, pulmonary venouscongestion worsens. Body weight increases incrementally, and fluids mayshift into the lower extremities. Medications for HF are designed tointerrupt the kidneys' hormonal responses to diminished perfusion, andthey also work to help excrete excess sodium and water from the body.However, an extremely delicate balance between these two biologicaltreatment modalities needs to be maintained, since an increase in bloodpressure (which relates to afterload) or fluid retention (which relatesto preload), or a significant change in heart rate due to atachyarrhythmia, can lead to decompensated HF. Unfortunately, thiscondition is often unresponsive to oral medications. In that situation,admission to a hospital is often necessary for intravenous diuretictherapy.

In medical centers, HF is typically detected using Doppler/ultrasound,which measures parameters such as SV, CO, and EF. In the homeenvironment, on the other hand, gradual weight gain measured with asimple weight scale is likely the most common method used to identifyCHF. However, by itself, this parameter is typically not sensitiveenough to detect the early onset of CHF—a particularly important stagewhen the condition may be ameliorated simply and effectively by a changein medication or diet.

SV is the mathematical difference between left ventricular end-diastolicvolume (EDV) and end-systolic volume (ESV), and represents the volume ofblood ejected by the left ventricle with each heartbeat; a typical valueis about 70-100 mL. CO is the average, time-dependent volume of bloodejected from the left ventricle into the aorta and, informally,indicates how efficiently a patient's heart pumps blood through theirarterial tree; a typical value is about 5-7 L/min. CO is the product ofHR and SV.

CHF patients—particular those suffering from systolic HF—may receiveimplanted devices such as pacemakers and/or cardioverter-defibrillatorsto increase EF and subsequent blood flow throughout the body. Thesedevices may include circuitry and algorithms to measure the electricalimpedance between different leads of the device. Some implanted devicesprocess this impedance to calculate a “fluid index”. As thoracic fluidincreases in the CHF patient, the impedance typically is reduced, andthe fluid index increases.

4. Clinical Solutions

Many of the above-mentioned parameters can be used as early markers orindicators that signal the onset of CHF. EF is typically low in patientssuffering from this chronic disease, and it can be further diminished byfactors such as a change in physiology, an increase in sodium in thepatient's diet, or non-compliance with medications. This is manifestedby a gradual decrease in SV, CO, and SYS that typically occurs betweentwo and three weeks before hospitalization becomes necessary to treatthe condition. As noted above, the reduction in SV and CO diminishesperfusion to the kidneys. These organs then respond with a reduction intheir filtering capacity, thus causing the patient to retain sodium andwater and leading to an increase in intravascular volume. This, in turn,leads to congestion, which is manifested to some extent by a build-up offluids in the patient's thoracic cavity (e.g. TFC). Typically, adetectable increase in TFC occurs about 1-2 weeks before hospitalizationbecomes necessary. Body weight increases after this event (typically bybetween three and five pounds), thus causing fluids to shift into thelower extremities. At this point, the patient may experience an increasein both HR and RR to increase perfusion. Nausea, dyspnea, and weightgain typically grow more pronounced a few days before hospitalizationbecomes necessary. As noted above, a characteristic of decompensated HFis that it is often unresponsive to oral medications; thus, at thispoint, intravenous diuretic therapy in a hospital setting often becomesmandatory. A hospital stay for intravenous diuretic therapy typicallylasts about 4 days (costing several thousands of dollars per day, ormore), after which the patient is discharged and the above-describedcycle may start over once again.

Such cyclical pathology and treatment is physically taxing on thepatient, and economically taxing on society. In this regard, CHF andESRD affect, respectively, about 5.3 million and 3 million Americans,resulting in annual healthcare costs estimated at $45 billion for CHFand $35 billion for ESRD. CHF patients account for approximately 43% ofannual Medicare expenditures, which is more than the combinedexpenditures for all types of cancer. Somewhat disconcertingly, roughly$17 billion of this is attributed to hospital readmissions. CHF is alsothe leading cause of mortality for patients with ESRD, and thisdemographic costs Medicare nearly $90,000/patient annually. Thus, thereunderstandably exists a profound financial incentive to keep patientssuffering from these diseases out of the hospital. Starting in 2012,U.S. hospitals have been penalized for above-normal readmission rates.Currently, the penalty has a cap of 1% of payments, growing to over 3%in the next 3 years.

Of some promise, however, is the fact that CHF-related hospitalreadmissions can be reduced when clinicians have access to detailedinformation that allows them to remotely titrate medications, monitordiet, and promote exercise. In fact, Medicare has estimated that 75% ofall patients with ESRD and/or CHF could potentially avoid hospitalreadmissions if treated by simple, effective programs.

Thus, in order to identify precursors to conditions such as CHF andESRD, physicians can prescribe physiological monitoring regimens topatients living at home. Typically, such regimens require the use ofmultiple standard medical devices, e.g. blood pressure cuffs, weightscales, and pulse oximeters. In certain cases, patients use thesedevices daily and in a sequential manner, i.e. one device at a time. Thepatient then calls a central call center to relay their measuredparameters to the call center. In more advanced systems, the devices arestill used in a sequential manner, but they automatically connectthrough a short-range wireless link (e.g. a Bluetooth® system) to a“hub,” which then forwards the information to a call center. Often, thehub features a simple user interface that presents basic questions tothe patient, e.g. questions concerning their diet, how they are feeling,and whether or not medications were taken.

For such monitoring to be therapeutically effective, it is important forthe patient to use their equipment consistently, both in terms of theduration and manner in which it is used. Less-than-satisfactoryconsistency with the use of any medical device (in terms of durationand/or methodology) may be particularly likely in an environment such asthe patient's home or a nursing home, where direct supervision may beless than optimal.

SUMMARY OF THE INVENTION

In view of the foregoing, it would be beneficial to provide a monitoringsystem that is suitable for home use. Particularly valuable would be asystem that is wireless and conveniently measures a collection of vitalsigns and hemodynamic parameters. Ideally, such a system would be easyto use, would improve measurement consistency, and feature a simple formfactor that integrates into the patient's day-to-day activities. Amonitoring system according to the invention, which facilitatesmonitoring a patient for HF, CHF, ESRD, cardiac arrhythmias, and otherdiseases, is designed to achieve this goal.

The inventive device described herein is a handheld device featuring anintegrated form factor that fits in a patient's hand and measures allvital signs and some hemodynamic parameters from the human body. Ittransmits information it measures through a wireless interface to aweb-based system, where it can be analyzed by a clinician to helpdiagnose a patient.

The inventive device and measurement methodologies are based in part onthe discovery that the bio-impedance signals (e.g. TBI waveforms) usedto determine vital signs and hemodynamic parameters can be measured overa conduction pathway that extends from the patient's wrist to a locationon their thoracic cavity, e.g. their chest or belly button. (Additionalconduction pathways we have discovered to be suitable include those thatextend from the wrist to the torso, legs, opposing arm, or neck.) Theform factor of the handheld device described herein accommodates suchmeasurements with a system that is comfortable, easy to use, andincludes re-usable electrodes to reduce costs. Measurements made by thehandheld device suitably use the belly button as a ‘fiducial’ marker, asdescribed in detail below. This location, which is present on nearly allpatients, facilitates consistent, daily measurements that reduce errorsdue to positioning that normally impact impedance measurements. Othermeasurement locations, such as a nipple, mole or other birthmark, elbow,wrist joint, etc., may also be used as a fiducial marker. What is mostimportant is that the patient positions the device consistently from onemeasurement to another. In this and other ways, the handheld deviceprovides an effective tool for characterizing patients with chronicdiseases, such as CHF, ESRD, and hypertension.

In one aspect, the invention provides a system for measuringbio-impedance waveforms (e.g. TBI waveforms) from a patient. The systemfeatures a rigid housing having a first portion configured to contactthe patient's wrist and a second portion, integrated with the firstportion and configured to be held against the patient's thoracic cavity.The rigid housing also encloses a circuit board. The first portionincludes a first pair of electrodes and the second portion includes asecond pair of electrodes, wherein one of the electrodes in each pair isconfigured to inject an electrical current into the patient's wrist ortorso, and the other electrode in each pair is configured to measure avoltage associated with the injected electrical current. An electricalsystem disposed on the circuit board receives signals from the first andsecond pair of electrodes, and processes them to determine atime-dependent bio-impedance waveform. A processing system disposed onthe circuit board processes the bio-impedance waveform to determine aphysiological parameter.

In another aspect, the invention provides a method for monitoring abio-impedance waveform from a patient. The method includes the followingsteps: 1) wearing or holding a handheld device configured, for example,as described above, with a first pair of electrodes contacting thewrist; 2) at the same time, contacting a region on the patient'sthoracic cavity with another electrode-bearing portion of the handhelddevice, so that an electrode in the first pair of electrodes injects anelectrical signal into the patient's wrist and an electrode in thesecond pair of electrodes injects an electrical signal into thepatient's thoracic cavity; 3) measuring a time-dependent waveform byprocessing a voltage measured by an electrode in each of the first andsecond pairs of electrodes; and 4) processing the voltage to determinethe bio-impedance waveform.

In another aspect, the invention provides a system for measuring vitalsigns and hemodynamic parameters from a patient. Here, the inventionfeatures a form factor generally similar to that described above, exceptthat it includes a third portion for receiving one of the patient'sfingers, preferably of the hand used to hold or wear the device. Thefirst and second portions include pairs of electrodes, as describedabove. The third portion features an optical system having a lightsource and a photodetector. The overall system includes an electricalsystem that processes signals from the electrodes, as described above,to generate bio-impedance and electrocardiogram waveforms. The systemalso receives a signal from the photodetector and processes it todetermine a photoplethysmogram waveform. A processing system disposed ona circuit board processes: 1) the bio-impedance waveform to determine anSV; 2) the electrocardiogram waveform to determine a HR; and 3) thephotoplethysmogram waveform to determine an SpO2 value.

In another aspect, the invention provides a method for monitoring vitalsign values from a patient. The method includes steps similar to thosedescribed above along with additional steps of: 1) inserting one of thepatient's fingers into an opening having an optical system, whichoptical system comprises a light source and a photodetector; 2)processing a signal measured by the photodetector to determine aphotoplethysmogram waveform; 3) additionally determining bio-impedanceand electrocardiogram waveforms; 4) analyzing the bio-impedance waveformto determine SV; 5) analyzing the electrocardiogram waveform todetermine HR; and 6) analyzing the photoplethysmogram waveform todetermine an SpO2 value.

In yet another aspect, the invention provides a system for determiningblood pressure using a handheld device as described above. In thisaspect, the invention includes a handheld sensor that is generallysimilar to that described above. The handheld sensor also includes aprocessing system disposed on the circuit board and configured to: 1)process the bio-impedance waveform to determine a first fiducial point;2) process the electrocardiogram waveform to determine a second fiducialpoint; 3) process the first and second fiducial points to determine apulse transit time; and 4) process the inverse of the transit time and apre-determined blood pressure calibration to determine the bloodpressure value.

In exemplary embodiments, the blood pressure calibration includes valuesof SYS, DIA, and MAP. In other embodiments, the calibration includes apatient-specific relationship between a transit time and blood pressure.In still other embodiments, the blood pressure calibration includes bothsets of parameters, e.g. initial blood pressure values and thepatient-specific relationship between a transit time and blood pressure.

Typically, the handheld device includes a wireless transmitter forsending and receiving information to/from another wireless device, e.g.,for use in connection with the blood pressure calibration. For example,the patient's weight may be sent to the device wirelessly from a digitalscale. In preferred embodiments the transmitter is based on Bluetooth®or 802.11.

In another aspect, the invention features a handheld device, used tomeasure various biometric parameters, in which inflatable structures arecovered with electrically conductive material. This allows thestructures to sense pressure (including pressure oscillations) as wellas to function as current-injecting or voltage-sensing electrodes.

In exemplary embodiments according to this aspect of the invention, theinflatable structures include a bladder that can be filled, e.g., with afluid such as air, and the handheld device includes a pressure-deliverysystem including a pump. The pump connects to the bladder and, inembodiments, a valve, and it is configured to pump air into the bladderwhen the pump is activated. A pressure sensor connects to the bladderand is configured to measure a pressure within the bladder.

Suitably, the processing system features computer code that analyzes theset of pressure values to determine the blood pressure value. Thecomputer code can run on, e.g., a microcontroller or microprocessor. Forexample, the pressure values can be a set of pressure-dependentoscillations that depend on the patient's blood pressure, and thecomputer code can analyze these to determine a blood pressure value.Typically, each pressure-dependent oscillation in the set ofpressure-dependent oscillations is characterized by a pressure andamplitude value, and the computer code is further configured todetermine the pressure-dependent oscillation having a maximum amplitudevalue. From this the system calculates the MAP. In related embodiments,the computer code is further configured to determine SYS from a firstpressure-dependent oscillation characterized by an amplitude that, whendivided by the maximum amplitude of the pressure-dependent oscillations,is substantially equivalent to a first pre-determined ratio (typicallybetween 0.4-0.8, and most preferably about 0.6). In yet another relatedembodiment, the computer code is further configured to determine DIAfrom a second pressure-dependent oscillation characterized by anamplitude that, when divided by the maximum amplitude of thepressure-dependent oscillations, is substantially equivalent to a secondpre-determined ratio (typically between 0.4-0.8, and most preferablyabout 0.7).

In embodiments, the set of pressure-dependent oscillations are measuredwhile the pressure-delivery system inflates or deflates the flexiblemember.

The handheld device features an electrical impedance system having atleast four electrodes, at least one of which is configured to inject anelectrical current into the patient's body and at least one of which isconfigured to measure a signal induced by the injected electricalcurrent and representative of biological impedance. A wireless systemwithin the handheld device receives an SV calibration value. An internalprocessing system receives signals from the electrical impedance systemand converts them into a set of impedance values, and analyzes the setof impedance values and the SV calibration to calculate SV.

In embodiments, the SV calibration includes a value representing thepatient's weight, height, body composition, and/or age. These values areused to calculate a volume conductor, described in more detail below.

In embodiments, the processing system features computer code configuredto analyze the set of impedance values to determine the stroke volumevalue. For example, the computer code can calculate a derivative of theset of impedance values to determine a dΔZ(t)/dt waveform, from which itcalculates a maximum value or an area of a pulse therein. The computercode can also analyze the dΔZ(t)/dt waveform to determine an ejectiontime or a baseline impedance (Z₀) value. The computer code can thenprocess these values to determine SV using Eq. 1:

$\begin{matrix}{{SV}\text{\textasciitilde}\frac{\left( {d\;\Delta\;{{Z(t)}/{dt}}} \right)_{\max}}{Z_{o}} \times {LVET}} & (1)\end{matrix}$or, alternatively, using Eq. 2:

$\begin{matrix}{{SV}\text{\textasciitilde}\sqrt{\frac{\left( {d\;\Delta\;{{Z(t)}/{dt}}} \right)_{\max}}{Z_{o}}} \times {LVET}} & (2)\end{matrix}$

In embodiments, the handheld device (wirelessly) receives a weight valuefrom a weight-measuring device, such as a scale. The processing systemcan then use the weight to determine SV from the equation:

$\begin{matrix}{{SV} = {V_{c} \times \frac{\left( {d\;\Delta\;{{Z(t)}/{dt}}} \right)_{\max}}{Z_{o}} \times {LVET}}} & (3)\end{matrix}$or, alternatively, using Eq. 4:

$\begin{matrix}{{SV} = {V_{c} \times \sqrt{\frac{\left( {d\;\Delta\;{{Z(t)}/{dt}}} \right)_{\max}}{Z_{o}}} \times {LVET}}} & (4)\end{matrix}$where V_(c) is a volume conductor calculated from the value of weightand/or body composition.

In still other aspects, the system calculates CO by also measuring HR asdescribed below (e.g. using an ECG waveform), and then collectivelyprocessing SV and HR (e.g., by taking the product) to determine CO.

In another aspect, the handheld device measures a PTT value from apatient, and then uses this and the blood pressure calibration todetermine the patient's blood pressure value.

In embodiments, the processing system features computer code configuredto: i) calculate a mathematical derivative of the impedance values todetermine a set of derivative values; and ii) determine a local maximumof the set of derivative values to determine the first pulsatilecomponent; and/or iii) determine a zero-point crossing of the set ofderivative values to determine the first pulsatile component. Thecomputer code may also be configured to: i) estimate the set ofderivative values using a mathematical function; and ii) analyze themathematical function to determine the first pulsatile component.

In embodiments, the computer code is configured to determine a localmaximum of the cardiac rhythm values to determine the second pulsatilecomponent, and the cardiac rhythm values are representative of an ECGwaveform. For example, the computer code can be configured to determinea QRS complex (e.g. calculate the Q or, more likely, R point) in the ECGwaveform to determine the second pulsatile component. It can alsofurther process the cardiac rhythm values to determine a heart ratevalue, e.g. by calculating a time interval separating the first andsecond R points.

The measurement system described herein has many advantages. Inparticular, it features and easy-to-use device that a patient can use tomeasure all their vital signs, complex hemodynamic parameters, and basicwellness-related parameters. Such ease of use may increase compliance,thereby motivating patients to use it every day. And with daily use, themeasurement system can calculate trends in a patient's physiologicalparameters, thereby allowing better detection of certain disease statesand/or management of chronic conditions such as CHF, diabetes,hypertension, COPD, and kidney failure.

Still other advantages should be apparent from the following detaileddescription, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a handheld device according to theinvention in use by a patient;

FIG. 2A is an illustration of the handheld device of FIG. 1 beingpressed against a patient's belly button and used to measure vital signsand hemodynamic parameters according to inventive aspects of theinvention;

FIG. 2B is a schematic diagram of the conduction pathway created whenthe handheld device of FIG. 1 is pressed against a patient's bellybutton;

FIG. 3 is a schematic perspective view of the handheld device of FIG. 1,including some of its internal electronic systems;

FIG. 4 is an exploded view of the handheld device of FIG. 3;

FIG. 5A is an end view of the handheld device of FIG. 1 showing itsinflatable electrodes inflated (to take a measurement);

FIG. 5B is an end view of the handheld device of FIG. 1 showing itsinflatable electrodes deflated (before and after a measurement);

FIG. 6 is a schematic drawing showing locations on the human body werethe handheld device can be used to measure physiological waveformshaving pulsatile components;

FIG. 7A is a plot of time-dependent ECG ΔZ(t) and PPG waveforms measuredwith the handheld device of FIG. 1;

FIG. 7B is a plot of time-dependent derivatives of the ΔZ(t) waveform(d(ΔZ(t))/dt) and PPG waveform (d(PPG)/dt) shown in FIG. 7A, along withmarkers indicating how VTT and PAT are calculated from these waveforms;and

FIG. 8 is a table showing various physiological conditions and how theycan be predicted by trends in certain physiological parameters.

DETAILED DESCRIPTION 1. Product Overview

A handheld device according to the invention integrates measurement ofall vital signs and some hemodynamic parameters from the human body intoa single, easy-to-use device. More specifically, the device measures thefollowing waveforms: 1) ECG; 2) pressure; 3) PPG; and 4) TBI. Digitalelectronics in the device process these waveforms to calculate thefollowing numerical information: 1) SYS, DIA, and MAP; 2) SpO2; 3) HRand HRV; 4) RR; 5) TEMP; 6) SV; 7) CO; and 8) FLUIDS. It uses permanent,reusable components (e.g. electrodes), and transmits numerical andwaveform information through a patient's mobile device to a web-basedsystem.

The handheld device supplants more complex prior systems that include,e.g., multiple devices to measure vital signs and hemodynamicparameters. For example, such prior systems may include a separate bloodpressure cuff, pulse oximeter, Holter monitor or patch-based system, andspirometer to measure vital signs. Determining hemodynamic parameterswith prior systems is typically more complicated, and may require abio-impedance and/or ultrasound machine to measure CO, SV, and FLUIDS.

Use of a single device, as opposed to multiple devices, can simplifyoperation and reduce the time required to measure the above-mentionedparameters. This, in turn, may increase the patient's compliance with aprescribed measurement regiment, as it is well established that dailyuse of devices that measure physiological parameters typically improvesas the time and complexity involved with using such devices decreases.By consistently collecting physiological information on a daily basis,systems using the handheld device can calculate trends in theinformation. Such trends may indicate the progression of certain diseasestates in a manner that is improved relative to one-time measurements ofcertain parameters. For example, a value of FLUIDS corresponding to 15Ohms, or an SV corresponding to 75 mL, has little value taken inisolation. But if these parameters decrease by 20% over a period of afew days, it can indicate that the patient's heart is pumping blood in aless efficient manner (as indicated by the SV), which in turn decreasesperfusion of the patient's kidneys and causes them to retain more fluids(as indicated by the FLUIDS level). Trends such as these can indicate,for example, the onset of CHF. Similar, trends in BP can indicate aworsening in hypertension or hypotension. Indeed, most disease statesare indicated by trends in one or, more commonly, multiple physiologicalparameters. The handheld device provides a simple solution for measuringthese parameters and their trends.

As shown in FIG. 1, a handheld device 100 according to the inventionfits comfortably in a patient's left or right hand 102. The device 100includes a generally C-shaped or U-shaped, wrist-receiving first portion104 at its lower end with a space or opening configured to receive thepatient's wrist. The space or opening is formed between a pair ofgenerally parallel, spaced-apart walls or “wings” 101 a, 101 b, whichextend from a base portion 101 c of the wrist-receiving portion 104 andsupport an inflatable pressure-cuff system and a pair of clothelectrodes, not visible in FIG. 1 but described more fully below.Suitably, the cloth electrodes are coincident with the pressure-cuffsystem in that they are formed from conductive, stretchable fabric thatoverlies one or more inflatable bladders.

A second, finger-receiving cavity portion 105 located at an opposite endof the device has an opening which is configured and positioned toreceive the distal end of the patient's thumb when the device is held,as shown in FIGS. 1 and 2A. In alternate embodiments, the opening couldbe configured and positioned to receive the distal end of other digitsof the patient's hand; however, positioning the opening along thelateral midline of the device so as to receive the user's thumb, andwith the opening facing toward the wrist, makes it easier to grasp thedevice and insert one's thumb into the opening, as well as enabling thedevice 100 to be used with either hand. The cavity portion 105 houses anoptical system—part of the pulse oximetry subsystem of the device100—featuring light-emitting diodes (LEDs) that operate in the red (660nm) and infrared (908 nm) spectral regions. A ‘neck’ 106 surrounds aninternal circuit board and connects the C-shaped first portion 104 andthe second, cavity portion 105. The neck 106 serves as a grip for thepatient to hold the device, and may included additional electrodes, asdescribed in more detail below. Mechanical and electrical components ofthese systems are explained in more detail with respect to FIG. 3.

To take a physiological measurement, as shown in FIG. 1, using theirhand 102 the patient grasps the handheld device 100 by its neck 106;inserts their thumb 107 into the opening in the cavity portion 105; andinserts their wrist 109 into the opening or space in the C-shaped firstportion 104. The patient gently wraps their fingers around the extendedneck 106 so that the handheld device 100 is secure in their hand 102.

As shown in FIG. 2A, the patient simultaneously touches a bottom surface110 of the handheld device 100 (e.g., an exposed, lower surface of base101 c) against bare skin near their belly button 120. The belly buttonserves as a good ‘fiducial’ marker that the patient can use daily as ameasurement location. Alternatively, a permanent marker on the patient'sbody, e.g. their nipples, could also be used as a fiducial marker fortaking measurement. The exposed bottom surface 110 of the handhelddevice 100 includes a pair of outwardly facing cloth electrodes (shownin more detail in FIGS. 3 and 4) that are similar to those included inthe C-shaped first portion 104. As illustrated in FIG. 2B, with thisconfiguration of the handheld sensor 100 and method of positioning thehandheld sensor 100 against the body, two pairs of electrodessimultaneously and respectively contact locations 250A, 250B on thewrist (i.e., a distal portion of the patient's arm) and locations 260A,260B on the belly of the patient 125. This establishes a relatively longconduction pathway 210, extending from the wrist, along the arm, andacross the thoracic cavity and over which the handheld device 100 canmeasure ECG and TBI waveforms. More particularly, the conduction pathway210, for example, extends from the radial and ulnar arteries in thepatient's wrist, through the brachial artery, sub-clavian artery nearthe shoulder, and finally through the aorta (which is the largest arteryin the body) and the heart. Depending on preferences, the exposed,outwardly facing electrodes could be positioned somewhere other than thebottom surface 110 of the sensor as a function of human anatomy andbiomechanics, to facilitate bringing the exposed electrodes into contactwith some other portion on the body beside the belly button or thenipple, e.g., the torso, the legs, the opposing arm, or the neck.

The handheld device described herein demonstrates that TBI waveformsmeasured with electrodes contacting the wrist have improvedsignal-to-noise ratios compared to waveforms measured with electrodescontacting the hands and/or fingers. Typically waveforms with relativelyhigh signal-to-noise ratios yield more accurate measurements. For thisreason, the handheld device described herein may be particularlyeffective in measuring parameters that are extracted from TBI waveforms,e.g. SV and CO. Without being bound by any theory, this may be becausethe wrist encloses blood-passing arteries (radial, ulnar) that arerelatively large and uncomplicated compared to those in the hand. Thussuch arteries are likely to yield TBI waveforms with relatively highsignal-to-noise ratios.

The patient holds the handheld device 100 in this position for about 30seconds, during which period of time the onboard microprocessordetermines the various parameters of interest. When the measurement iscomplete an internal microprocessor controls a user-interface device(e.g., an LED or buzzer) to notify the patient. Once this occurs, aninternal Bluetooth® transmitter in the handheld device 100 transmitsnumerical and waveform information to the patient's mobile device (notshown in the figure), which forwards it to a web-based system. There, aclinician, the patient, family member, etc. can review the information.

FIGS. 3 and 4 illustrate the handheld device's measurement electronicsand internal components in more detail. In general, a housing of thehandheld device 100 is constructed from two generally symmetric, rightand left halves 177A, 177B, which are joined together along alongitudinal midline. The housing halves 177A, 177B are suitably formed(e.g., injection molded) from a rigid material, e.g., medical-gradeplastic. A circuit board 130 is housed within an internal space formedby the right and left halves 177A, 177B of the handheld device'shousing, primarily within the neck 106, and supports the electronicsthat drive each measurement. A battery pack 170, including tworechargeable lithium-ion batteries, powers the system. The batteries canbe recharged through a standard USB connector (not shown in the figure)that connects through a cable to an AC/DC adaptor plugged into a walloutlet or, depending on power requirements, a USB port of a personalcomputer.

The handheld sensor 100 also includes an additional electrode 111 thatis typically used as a drive electrode to reduce 60 Hz noise typicallycaused by common mode interference. This component is located on anouter portion of the neck 106 so as to make contact with the patient'sskin (e.g. on their palms and/or fingers) when they grasp the neck 106.Typically, such an electrode and associated electrical circuitry isreferred to as a ‘right leg drive’. Right leg drive circuitry is knownin the art, and is used to eliminate common-mode interference noise byactively canceling the interference. A second electrode 113, alsolocated on an outer portion of the neck 106 so as to make contact withthe patient's skin when they grasp the neck 106, may also be used toimprove the performance of the handheld device's right leg drivecircuitry.

The upper portion of the circuit board 130 extends to within the cavityportion 105 and includes a dual-emitting LED 132, which generates redand infrared optical wavelengths in the 660 nm and 908 nm region, and aphotodetector (e.g., photodiode) 134. These components measure PPGwaveforms using both red and infrared radiation, as is generally knownin the art, but quite advantageously from one of the digits (e.g., thethumb) of the hand with which the patient holds the handheld sensor.This makes for a highly compact, easy-to-use, comprehensive device. Adigital system within the circuit board processes the waveforms todetermine SpO2. Generally speaking, such measurement is described inmore detail in the following co-pending patent applications, thecontents of which are incorporated herein by reference: “NECK-WORNPHYSIOLOGICAL MONITOR,” U.S. Ser. No. 62/049,279, filed Sep. 11, 2014;“NECKLACE-SHAPED PHYSIOLOGICAL MONITOR,” U.S. Ser. No. 14/184,616, filedFeb. 19, 2014; and “BODY-WORN SENSOR FOR CHARACTERIZING PATIENTS WITHHEART FAILURE,” U.S. Ser. No. 14/145,253, filed Dec. 31, 2013, andPHYSIOLOGICAL MONITORING SYSTEM FEATURING FLOORMAT AND WIRED HANDHELDSENSOR. In general and as explained in greater detail in theseincorporated references, during an SpO2 measurement, the digital systemalternately powers red and infrared LEDs within the dual-emitting LED132. This process generates two distinct PPG waveforms. Using bothdigital and analog filters, the digital system extracts AC and DCcomponents from the red (RED(AC) and RED(DC)) and infrared (IR(AC) andIR(DC)) PPG waveforms, which the digital system then processes todetermine SpO2, as described in the above-referenced patentapplications.

To measure TEMP, the handheld device 100 includes an infraredtemperature sensor 136, which is mounted to an upper, forward-mostportion of the circuit board 130. The infrared temperature sensordetects temperature “looking outwardly” from an upper, outer,forward-facing “nose” portion 138 of the cavity portion 105. Morespecifically, to measure TEMP, the handheld device 100 is held close tothe patient's ear so that the outer portion 138 is adjacent to orpressed up against either the left or right ear. Because the temperaturesensor is positioned where it is, the patient can take a temperaturereading with the same device used to measure the other physiologicalparameters, and without even having to remove the device from his or herhand to do so. In this configuration, the infrared temperature sensor136 detects infrared radiation (e.g. blackbody radiation) emitted frominside the ear, which it then converts to a temperature value usingtechniques known in the art. Suitably, the temperature sensor 136 is afully digital system, meaning it receives the infrared radiation with aninternal photodetector and, using an internal digital system, convertsthis to a temperature value that it sends through a serial interface(e.g. one based on a conventional UART or I2C interface) for follow-onprocessing.

A multi-color status LED assembly 175 indicates when the device turnson, a measurement is being taken, a measurement is complete, and dataare being transmitted through Bluetooth. The multi-color status LEDassembly 175 can change color and blink at different frequencies toindicate these states.

The C-shaped, wrist-receiving portion 104 is configured to measurephysiological parameters using two complementary measurement modalities.According to one modality, the C-shaped portion measures BP, e.g. SYS,DIA, and MAP, by direct sensing of pressure. To that end, thewrist-receiving portion 104 includes a pair of inflatable/deflatable,elastomeric bladders 140A,B, which are mounted on or supported by thetwo generally parallel, spaced-apart walls or wings 101 a, 101 b thatextend from the base 101 c of the wrist-receiving portion 104; the wallsform the space or opening in which the patient's wrist is received, asnoted above and as illustrated in FIGS. 1 and 2A. (Other shapes of thebladder-supporting walls are also acceptable. For example, even acompletely circular, wrist-surrounding ring-shaped structure throughwhich the patient would insert their arm could be provided.) Thebladders 140A,B are configured and arranged to inflate inwardly, i.e.,into the wrist-receiving space or opening, as illustrated in FIGS. 5Aand 5B. A pair of plastic supports 163A, 163B hold the inflatablebladders 140A,B in place on their respective walls. Additionally, theplastic supports 163A, 163 B clamp down on stretchable cloth electrodes150A,B, addressed below, which overlie the bladders.

A small pneumatic pump system 142, controlled by the digital system onthe circuit board 130, inflates the bladders 140A,B to measure BP. Ingeneral, such pump systems are known in the art for use in connectionwith blood-pressure monitors such as those typically sold for home use.The pump system 142 includes a diaphragm pump; a solenoid-controlledvalve to maintain or release pressure within the bladders; and suitableairline tubing leading into the bladders.

Gradual inflation of the bladders 140A,B slowly compresses the patient'sradial artery. As it compresses, heartbeat-induced blood-flow within theartery generates slight pressure pulsations. These create a smallpressure increase in the bladders that are detected by apressure-measuring system (not shown in the figure) within the circuitboard 130, as known in the art. This yields a pressure waveform thatfeatures amplitudes of the pressure pulsations plotted against thepressure applied by the inflatable bladders 140A,B. The pressurewaveform typically features a bell-shaped curve when the amplitude ofeach pressure pulsation is plotted against the pressure applied. Thedigital system processes the bell-shaped curve to determine bloodpressure according to the well-known technique of oscillometry. Such atechnique is described in detail in the following co-pending patentapplications, the contents of which have been previously incorporatedherein by reference: “NECK-WORN PHYSIOLOGICAL MONITOR,” U.S. Ser. No.62/049,279, filed Sep. 11, 2014; “NECKLACE-SHAPED PHYSIOLOGICALMONITOR,” U.S. Ser. No. 14/184,616, filed Feb. 19, 2014; and “BODY-WORNSENSOR FOR CHARACTERIZING PATIENTS WITH HEART FAILURE,” U.S. Ser. No.14/145,253, filed Dec. 31, 2013, and PHYSIOLOGICAL MONITORING SYSTEMFEATURING FLOORMAT AND WIRED HANDHELD SENSOR. To summarize, MAPcorresponds to the applied pressure that yields the maximum amplitude ofthe bell-shaped curve. SYS and DIA are determined, respectively, fromapplied pressures that yield well-defined amplitudes on thehigh-pressure and low-pressure sides of MAP. More specifically, SYStypically corresponds to the applied pressure that yields a pulseamplitude on the high-pressure side of MAP that, when divided by thepulse amplitude corresponding to MAP, has a ratio of about 0.4. DIAtypically corresponds to the applied pressure that yields a pulseamplitude on the low-pressure side of MAP that, when divided by thepulse amplitude corresponding to MAP, has a ratio of 0.6. Other ratioscan also be used to calculate SYS and DIA according to oscillometry.

During inflation, patches of conductive fabric disposed on the outer,wrist-contacting surface of the bladders 140A,B detect bio-electricsignals. These are processed by analog circuitry associated on thecircuit board 130 to generate ECG and TBI waveforms, as described inmore detail below.

The handheld device 100 can also measure blood pressure according to analternative direct-pressure-based technique. This technique involvesmonitoring PPG waveforms generated by the SpO2 measuring system (i.e.,by either red or infrared wavelengths emitted by the dual-emitting LED132 and detected by the photodetector 134) while the inflatable bladders140A,B apply pressure to the patient's radial artery. Here, the appliedpressure slowly reduces blood flow through the artery, causingheartbeat-induced PPG-waveform pulsations (i.e. pulsations in theRED(AC) or IR(AC) components of the PPG waveforms) to slowly increase,and then gradually decrease. As with oscillometry, the maximum amplitudeof the pulsations typically corresponds to an applied pressure equal toMAP. The pulsations are completely eliminated when the applied pressureis equal to SYS, since at this pressure the radial artery is fullyoccluded, thus ceasing all blood flow. DIA can be determined from MAPand SYS using equations described in the above-referenced patentapplications, the contents of which have been previously incorporatedherein by reference.

The other modality by which the C-shaped, wrist-receiving portion 104measures physiological parameters is by processing bioelectric signals.In particular, the two pairs of cloth electrodes are provided to measurebioelectric signals, which then pass to the associated analog circuitryprovided on the circuit board 130. The analog circuitry processes thesignals to generate ECG and TBI waveforms, which the analog-to-digitalconverter and microprocessor then, respectively, digitize and process todetermine HR and HRV, RR, SV, CO, and TFC. As indicated above, one pairof electrodes is located within the C-shaped wrist-receiving portion104, and these electrodes are arranged to contact the patient's wristwhen it is received within the space or opening of that portion. Theother pair of cloth electrodes 160A, 160B is located along the bottomsurface 110 of the wrist-receiving portion 104. During use theelectrodes 160A, 160B contact a second portion of the patient (e.g.belly button) to establish the conduction pathway 210 as describedabove.

Believed to be unique to the handheld sensor 100, the wrist-contactingelectrodes 150A, 150B are coincident with (i.e., overlie) the inflatablebladders 140A, 140B, respectively, such that the overall system includeswhat are effectively inflatable electrodes. As a result, when thebladders are inflated in connection with measuring BP via direct,mechanical measurement of pressure, the electrodes are pressed firmlyagainst the patient's skin, thereby enhancing electrical contact andaccuracy/reliability of the electrophysiological measurements beingtaken. Additionally, such an arrangement facilitates the compact,self-contained form factor of the handheld sensor 100.

To this end, and as shown in more detail in FIGS. 5A and 5B, theelectrodes 150A, 150B are formed from a stretchable, conductive fabricthat is stretched over the inflatable bladders. In general, theelectrode material is conductive fabric that has conductive elementsinterwoven in an elastic material. Resistivity is essentially 0 Ohms inboth stretched and unstretched configurations. Suitably, the fabric isable to stretch by at least 25% along at least one dimension when theinflatable bladder is inflated, and preferably it is able to stretch byroughly 50% of its original dimension when force is applied to it.Although it is not required, the torso-contacting or belly-contactingelectrodes 160A, 160B may also be formed from the same stretchablematerial. In this way all the electrodes 150A, 150B, 160A, 160B) have asimilar skin/electrode impedance, which can be advantageous for ECG andTBI measurements.

As described above, the electrodes 150A,B and 160A,B are used to measuretime-dependent ECG and TBI waveforms, and the digital system within thecircuit board 130, in turn, processes the ECG and TBI waveforms todetermine the above-enumerated values (HR and HRV, RR, SV, CO, and TFC).During a measurement, one electrode (e.g., 150B) in the C-shapedwrist-receiving portion 104 and one electrode (e.g., 160B) on the bottomsurface 110 measure signals that the digital system processes usingdifferential amplification to determine an ECG waveform. This waveformfeatures heartbeat-induced pulses that, informally, mark the beginningof the cardiac cycle. Typically, the pulses include a sharp feature,called a QRS complex, which indicates electrical activity in the heart.The time separating neighboring QRS complexes is inversely related tothe patient's HR. Typically, HR is calculated from a collection of QRScomplexes spanning a short period of time, e.g. 30 seconds. Thevariation in heart rate determined during this period is the HRV, whichis known to relate to cardiac function.

The handheld device's bio-impedance measurement system “shares”electrodes with the ECG measurement system. For bio-impedance, oneelectrode (e.g., 150A) in the C-shaped wrist-receiving portion 104 andone electrode (e.g., 160A) on the bottom surface 110 of the deviceinject a high-frequency (e.g., 100 kHz), low-amplitude (e.g., 6 mA)current into the patient's body. The current injected by the twoelectrodes 150A, 160A is out of phase by 180°. The other two electrodes(e.g., 150B, 160B) measure a voltage that, with follow-on processing,indicates the resistance (or impedance) encountered by the injectedcurrent. The voltage relates to the resistance (or impedance) throughOhms Law. Typically, a bio-impedance circuit within the circuit boardmeasures TBI waveforms, which are separated into an AC waveform thatfeatures relatively high-frequency features (typically called ΔZ(t)),and a DC waveform that features relatively low-frequency features(typically called Z₀). This technique for measuring ΔZ(t) and Z₀, calledbio-impedance, is described in detail in the following co-pending patentapplications, the contents of which have been previously incorporatedherein by reference: “NECK-WORN PHYSIOLOGICAL MONITOR,” U.S. Ser. No.62/049,279, filed Sep. 11, 2014; “NECKLACE-SHAPED PHYSIOLOGICALMONITOR,” U.S. Ser. No. 14/184,616, filed Feb. 19, 2014; and “BODY-WORNSENSOR FOR CHARACTERIZING PATIENTS WITH HEART FAILURE,” U.S. Ser. No.14/145,253, filed Dec. 31, 2013, and PHYSIOLOGICAL MONITORING SYSTEMFEATURING FLOORMAT AND WIRED HANDHELD SENSOR.

Physiological processes within the body modulate ΔZ(t) and Z₀ waveformsgenerated by the handheld device's bio-impedance measurement system.Thus processing these waveforms can yield parameters that correspond tothe physiological processes. As shown in FIG. 2B, when used as describedabove on a patient 125, the handheld device injects current (indicatedby I1, I2) and detects voltage (indicated by V1, V2) over a conductionpathway 210 that extends from locations 250A, 250B near the patient'swrist to locations 260A, 260B near their belly button. The conductionpathway 210 passes through the patient's thoracic cavity, which containsvital organs such as the heart and lungs. Physiological processes thattake place within the thoracic cavity modulate the TBI waveform. Forexample, respiratory effort (i.e. breathing) changes the capacitance ofthe chest, thus imparting a series of low-frequency undulations(typically 5-30 undulations/minute) on the ΔZ(t) waveform. The handhelddevice's digital system processes these oscillations to determine RR.

Blood is a decent electrical conductor, and thus blood pumped by theheart's left ventricle into the aorta modulates impedance in thethoracic cavity 220 (as well as other regions spanned by the conductionpathway 201, e.g. the brachial artery located in the patient's bicep).These modulations manifest as heartbeat-induced cardiac pulses on theΔZ(t) waveform. They can be processed to determine SV as described indetail in the following co-pending patent applications, the contents ofwhich have been previously incorporated by reference: “NECK-WORNPHYSIOLOGICAL MONITOR,” U.S. Ser. No. 62/049,279, filed Sep. 11, 2014;“NECKLACE-SHAPED PHYSIOLOGICAL MONITOR,” U.S. Ser. No. 14/184,616, filedFeb. 19, 2014; and “BODY-WORN SENSOR FOR CHARACTERIZING PATIENTS WITHHEART FAILURE,” U.S. Ser. No. 14/145,253, filed Dec. 31, 2013, andPHYSIOLOGICAL MONITORING SYSTEM FEATURING FLOORMAT AND WIRED HANDHELDSENSOR. The handheld device determines CO, which is the product of SVand HR, using a simple calculation.

Fluids (e.g. TFC) also conduct the injected current. Thus, fluids thataccumulate in the thoracic cavity 220 affect the impedance within theconduction pathway 201 in a low-frequency (i.e. slowly changing) manner,and can be detected by processing the Z₀ waveform. Typically, the Z₀waveform features an average value of between about 10-30 Ohms, with 10Ohms indicating relatively low impedance and thus high fluid content(e.g. the patient is ‘wet’), and 30 Ohms indicating a relatively highimpedance and thus low fluid content (e.g. the patient is ‘dry’).Time-dependent changes in the average value of Z₀ can indicate that thepatient's fluid level is either increasing or decreasing. An increase influid level, for example, may indicate the onset of CHF.

2. Other Measurements—Bioreactance

Other measurement systems can be incorporated into the handheld device100. For example, the cloth electrodes 150A,B, 160A,B described above,coupled with an additional circuit that measures a phase change in theinjected current, can also be used to perform a measurement calledbio-reactance. During a bio-reactance measurement, the phase differencebetween the injected currents and the detected currents is measured bythe bio-reactance circuit and ultimately processed with the digitalsystem on the circuit board to generate a bio-reactance waveform. Thedifference in phase in the bio-reactance waveform is due to the currentbeing slowed down by the capacitive properties of cell membranes withinthe conduction pathway 210. The baseline phase difference, Φa, isestimated from the DC component of the bio-reactance waveform. Φa isused to calculate tissue composition, described in more detail below.The AC component of the waveform can be used to track respiration andcardiac function as described above.

Bio-reactance, when combined with bio-impedance, can be used to measurephysiological parameters related to body composition (e.g. fat, muscle,and fluid in the patient's body) and the progression of disease states.More specifically, bio-impedance and bio-reactance measurements analyzethe resistance and reactance of the user's tissue—along with biometricparameters such as height, weight and age—to generate accurate estimatesof the composition of the tissue in the abdomen, chest, and arm. Height,weight, and age, for example, can be input to the GUI of the patient'smobile device, and wirelessly transmitted to the handheld device forfollow-on analysis.

Φa and Z₀ are then used to calculate the resistance (Z₀ cos(Φa)) and thereactance (Z₀ sin(Φa)) of the tissue in the abdomen, chest, and rightarm. Resistance and reactance have been shown to be predictive of tissuecomposition. For example, fatty tissue is far more conductive thanfat-free tissue. Therefore, a tissue's resistance is largely governed bythe mass of the fat-free tissue present. This makes the inverse of atissue's resistance a good estimator of that tissue's fat-free mass.Similarly, cell membranes have capacitive properties that cause phasechanges in current that passes through the body. The greater theconcentration of cells in the tissue, the greater the change in phase.When coupled with resistance, reactance can thus distinguish changes infat from changes in fluid due to the differences in the cellularity offat and extracellular fluid. Specifically, it has been shown thatresistance and reactance—coupled with height, weight and age—can predictfat-free mass and body-fat mass as accurately as the “gold-standard”method—air displacement plethysmography. This is described in thefollowing journal article, the contents of which are incorporated hereinby reference: Body fat measurement by bioelectrical impedance and airdisplacement plethysmography: a cross-validation study to designbioelectrical impedance equations in Mexican adults; Nutrition Journal;6: (2007). When fat-free mass, body-fat mass, and weight are measured,the root cause of changes in weight can be identified. Changes in fluidretention can signal the onset or reoccurrence of numerous medicalconditions, such as CHF and ESRD. By measuring both reactance andresistance, the handheld device can distinguish changes in fluidretention from changes in tissue mass. This enables reliable tracking ofthis important parameter at home, on a daily basis.

3. Other Measurements—Pulse Transit Time

As shown in FIG. 6, the handheld device measures from a patient 190heartbeat-induced pulsatile components from the following waveforms: ECG250, TBI 252, pressure 254, and PPG 256. As indicated in the figure, thehandheld device samples pulsatile components in these waveforms alongdifferent portions of the patient's body, with each portion separatedfrom the source of the pulsatile components—the patient's heart—by asequentially increasing distance. For example, optics (LED 132,photodetector 134) within the finger-receiving cavity portion 105 of thehandheld device measure pulsatile components in the PPG waveform 256,sampled from arteries within the patient's thumb 266. The inflatablebladders in the C-shaped wrist-receiving portion 104, coupled withpressure-measuring electronics, sense pulsatile components from thepressure waveform 254 measured from the patient's wrist 264. Clothelectrodes and the bio-impedance (and optionally bio-reactance) circuitsmeasure pulsatile components in the ΔZ(t) waveform 252, which primarilysenses blood flow from the heart's left ventricle into the aorta 262.And the QRS complex of the ECG waveform 250 is a pulsatile componentthat indicates initial electrical activity in the patient's heart 260and, informally, marks the beginning of the cardiac cycle.

Thus detection and analysis of each of the above-described pulsatilecomponents indicates blood flow through the patient's body. Morespecifically, the digital system in the handheld component can analyzethe pulsatile components to determine parameters such as pulse arrivaltime (PAT), pulse transit time (PTT), and vascular transit time (VTT).Such transit times can be used, for example, to calculate bloodpressure, e.g. SYS, DIA, and MAP. This methodology is described in moredetail in the following co-pending patent applications, the contents ofwhich have been previously incorporated herein by reference: “NECK-WORNPHYSIOLOGICAL MONITOR,” U.S. Ser. No. 62/049,279, filed Sep. 11, 2014;“NECKLACE-SHAPED PHYSIOLOGICAL MONITOR,” U.S. Ser. No. 14/184,616, filedFeb. 19, 2014; and “BODY-WORN SENSOR FOR CHARACTERIZING PATIENTS WITHHEART FAILURE,” U.S. Ser. No. 14/145,253, filed Dec. 31, 2013, andPHYSIOLOGICAL MONITORING SYSTEM FEATURING FLOORMAT AND WIRED HANDHELDSENSOR.

To summarize, FIGS. 7A and 7B show the following time-dependentwaveforms, as measured by the handheld device: ECG (plot 300), ΔZ(t)(plot 302), PPG (plot 304), d(ΔZ(t))/dt (plot 306), and d(PPG)/dt (plot308). As shown in plots 300 and 302, individual heartbeats producetime-dependent pulses in both the ECG and ΔZ(t) waveforms. As is clearfrom the data, pulses in the ECG waveform precede those in the ΔZ(t)waveform. The ECG pulses—each featuring a sharp, rapidly rising QRScomplex—mark the beginning of the cardiac cycle.

ΔZ(t) pulses follow the QRS complex by about 100 ms and indicate bloodflow through arteries in the region of the body where the clothelectrodes make contact with the skin. During a heartbeat, blood flowsfrom the patient's left ventricle into the aorta; the volume of bloodthat leaves the ventricle is the SV. Blood flow periodically enlargesthis vessel, which is typically very flexible, and also temporarilyaligns blood cells (called erythrocytes) from their normally randomorientation. Both the temporary enlargement of the vessel and alignmentof the erythrocytes improves blood-based electrical conduction, thusdecreasing the electrical impedance as measured with ΔZ(t). Thed(ΔZ(t))/dt waveform (plot 306) shown in FIG. 7B is a first mathematicalderivative of the raw ΔZ(t) waveform, meaning its peak represents thepoint of maximum impedance change.

A variety of time-dependent parameters can be extracted from the ECG andTBI waveforms. For example, as noted above, it is well know that HR canbe determined from the time separating neighboring ECG QRS complexes.Likewise, left ventricular ejection time (LVET) can be measured directlyfrom the derivative of pulses within the ΔZ(t) waveform, and isdetermined from the onset of the derivatized pulse to the firstpositive-going zero crossing. Also measured from the derivatized pulsesin the ΔZ(t) waveform is (dΔZ(t))/dt)_(max), which is a parameter usedto calculate SV as described above.

The time difference between the ECG QRS complex and the peak of thederivatized ΔZ(t) waveform represents a pulse arrival time PAT, asindicated in FIGS. 7A and 7B. This value can be calculated from otherfiducial points, including, in particular, locations on the ΔZ(t)waveform such as the base, midway point, or maximum of theheartbeat-induced pulse. Typically, the maximum of the derivatizedwaveform is used to calculate PAT, as it is relatively easy to develop asoftware beat-picking algorithm that finds this fiducial point.

PAT correlates inversely to SYS, DIA, and MAP, which can be calculatedas described in the above-referenced patent applications usingpatient-specific slopes for SYS and DIA, measured during a calibrationmeasurement. (Such a measurement can, for example, be performed with theinflatable bladders and optical systems described above.) Without thecalibration, PAT only indicates relative changes in SYS, DIA, and MAP.The calibration yields both the patient's immediate values of theseparameters. Multiple values of PAT and blood pressure can be collectedand analyzed to determine patient-specific slopes, which relate changesin PAT with changes in SYS, DIA, and MAP. The patient-specific slopescan also be determined using pre-determined values from a clinicalstudy, and then combining these measurements with biometric parameters(e.g. age, gender, height, weight) collected during the clinical study.

In embodiments of the handheld device, waveforms like those shown inFIGS. 7A and 7B can be processed to determine PAT. The handheld devicecan use this parameter, combined with a calibration determined asdescribed above, to determine blood pressure without aphysical-pressure-applying mechanism. Typically PAT and SYS correlatebetter than PAT and DIA.

Pulse pressure (PP) can be used to calculate DIA from SYS, and can beestimated from either the absolute value of SV, SV modified by anotherproperty (e.g. LVET), or the change in SV. In the first method, a simplelinear model is used to process SV (or, alternatively, SV×LVET) andconvert it into PP. The model uses the instant values of PP and SV,determined as described above from a calibration measurement, along witha slope that relates PP and SV (or SV×LVET) to each other. The slope canbe estimated from a universal model that, in turn, is determined using apopulation study.

Alternatively, a slope tailored to the individual patient can be used.Such a slope can be selected, for example, using biometric parameterscharacterizing the patient as described above.

Here, PP/SV slopes corresponding to such biometric parameters aredetermined from a large population study and then stored in computermemory on the handheld device. When a device is assigned to a patient,their biometric data is entered into the system, e.g. using a GUIoperating on a mobile device, that transmits the data to the handhelddevice via Bluetooth®. Then, an algorithm processes the data and selectsa patient-specific slope. Calculation of PP from SV is explained in thefollowing reference, the contents of which are incorporated herein byreference: “Pressure-Flow Studies in Man. An Evaluation of the Durationof the Phases of Systole,” Harley et al., Journal of ClinicalInvestigation, Vol. 48, p. 895-905, 1969. As explained in thisreference, the relationship between PP and SV for a given patienttypically has a correlation coefficient r that is greater than 0.9,which indicates excellent agreement between these two properties.Similarly, in the above-mentioned reference, SV is shown to correlatewith the product of PP and LVET, with most patients showing an r valueof greater than 0.93 and the pooled correlation value (i.e., thecorrelation value for all subjects) being 0.77. This last valueindicates that a single linear relationship between PP, SV, and LVET mayhold for all patients.

More preferably, PP is determined from SV using relative changes inthese values. Typically, the relationship between the change in SV andchange in PP is relatively constant across all subjects. Thus, similarto the case for PP, SV, and LVET, a single, linear relationship can beused to relate changes in SV and changes in PP. Such a relationship isdescribed in the following reference, the contents of which areincorporated herein by reference: “Pulse pressure variation and strokevolume variation during increased intra-abdominal pressure: anexperimental study,” Didier et al., Critical Care, Vol. 15:R33, p. 1-9,2011. Here, the relationship between PP variation and SV variation for67 subjects displayed a linear correlation of r=0.93, which is anextremely high value for pooled results that indicates a single, linearrelationship may hold for all patients.

From such a relationship, PP can be determined from the impedance-basedSV measurement, and SYS can be determined from PAT. DIA can then becalculated from SYS and PP.

Another parameter, VTT, can be determined from pulsatile components inthe ΔZ(t) (or d(ΔZ(t))/dt) waveform and the PPG (or d(PPG)/dt) waveform.FIGS. 7A and 7B show in more detail how VTT is determined. It can beused in place of PAT to determine blood pressure, as described above.Using VTT instead of PAT in this capacity offers certain advantages,namely, lack of signal artifacts such as pre-injection period (PEP) andisovolumic contraction time (ICT), which contribute components to thePAT value but which are not necessarily sensitive to or indicative ofblood pressure.

In general, the overarching purpose of a handheld device according tothe invention, as described above, is to make daily measurements of awide range of physiological parameters that, in turn, can be analyzed todiagnose specific disease states. As described above, it is often thetime-dependent trends in the physiological parameters that provide thebest indication of such disease states. In general, it is a collectionof trends in multiple physiological parameters that often serve as thebest marker for the onset of disease states. In this regard, FIG. 8shows, for example, a table 400 indicating how trends in differentphysiological parameters can be used to diagnose disease states such ashypertension, cardiac disease, heart failure (including CHF), renalfailure (including ESRD), chronic obstructive pulmonary disease (COPD),diabetes, and obesity. In addition, the table 400 indicates how suchtrends may show beneficial progress to a population actively involved inexercise.

4. Other Embodiments

Other embodiments are within the scope of the invention. For example,measurement electronics used within the handheld device can be packagedin form factors that differ from those described above. Such formfactors should make measurements along a suitably long conductionpathway. This pathway can also be different than that described above.For example, it may begin in the chest (as opposed to the belly button)or shoulder, and terminate in the fingers (as opposed to the wrist).

The handheld device can also be coupled to other systems that measureother parameters from a patient. Here, ‘coupled’ typically meansinformation passes between the handheld device and the other systemsthrough a wired or, more preferably, wireless interface. For example,the device can be coupled to a weight-measuring device through aBluetooth® or WiFi® interface. The weight-measuring device can be astandard weight scale, or a ‘digital floormat’ as described in thefollowing co-pending patent applications, the contents of which havebeen previously incorporated herein by reference: “NECK-WORNPHYSIOLOGICAL MONITOR,” U.S. Ser. No. 62/049,279, filed Sep. 11, 2014;“NECKLACE-SHAPED PHYSIOLOGICAL MONITOR,” U.S. Ser. No. 14/184,616, filedFeb. 19, 2014; and “BODY-WORN SENSOR FOR CHARACTERIZING PATIENTS WITHHEART FAILURE,” U.S. Ser. No. 14/145,253, filed Dec. 31, 2013, andPHYSIOLOGICAL MONITORING SYSTEM FEATURING FLOORMAT AND WIRED HANDHELDSENSOR.

In other embodiments, the device may include a flexible or bendableneck, e.g., to accommodate various dimensions and/or geometries of thefingers relative to the hand. In such embodiments, the joint connectingthe finger-receiving, oximetry-sensor portion of the device and thewrist-receiving, inflatable-bladder portion of the device would house aflex circuit connecting the circuitry in the neck to that in the base ofthe device. The joint can be composed of an elastic material (e.g.rubber) such that the neck can be extended further and moved closer tothe bladder. Similarly, in still further embodiments, the walls or“wings” on which the inflatable bladders are supported could be joinedto the base or bottom of the wrist-receiving portion of the device bymore flexible joints. Since there is no circuitry within the walls orwings, no flex circuit would be required; instead a simple elasticmaterial (e.g., a solid rubber boot) would allow the wings to flex andbend outwards in order to accommodate patients of varying wrist size.

In further embodiments, the device may have a hinged oximetry sensor.The sensor would have a hinge near the tip of the thumb such that itclamps down on the patient's thumb (like a spring-loaded clothespin) andapplies a constant pressure to this appendage. This would ensure thatthe sensor accommodates patients of varying thumb size, and may alsoimprove the signal-to-noise ratio of the PPG waveform it measures.

In further embodiments, the device may include a cuff-like mechanismthat completely encircles the patient's wrist, instead of the wings orarms that only partially encircle it. The cuff could be composed of anelastic material (e.g. rubber) or an inelastic material (e.g. nylon)that wraps around the patient's wrist, with a fastening mechanism at thetop (e.g. Velcro, magnet). The circuitry would still be located in thebase of the cuff, and a rigid material (e.g. plastic) would house it forprotection. In other embodiments, the device may be entirely constructedof a flexible material (e.g. rubber), with rigid components only housingthe main circuitry and flex circuits linking the circuit in the cuff tothe circuit in the oximetry sensor. In other embodiments, the device maytake on more of a fingerless-glove-like form, covering the entire hand,wrist and thumb of the patient. This embodiment would still require somerigid material housing the main circuitry of the device and the oximetrysensor.

In still further embodiments, the device may have a wrist cuff and aflexible cord or wire connecting the optical sensor on the thumb. Thecord or wire could connect the oximetry sensor to the main circuitry inthe wrist cuff, similar to other embodiments. The wrist cuff would haveto fully enclose the patient's wrist, since it is no longer held inplace by the rigidity of the form factor. In this sense, it would need afastening mechanism (i.e. Velcro, magnet) to hold the cuff close aroundthe patient's wrist.

In other embodiments the exterior electrodes could be positioned tofacilitate making contact with other parts of the body to obtain thesame measurements. For example, the exterior electrodes could be pressedagainst the patient's chest. In other embodiments, the electrodes couldbe constructed with another conductive material other than foam orinflatable rubber covered in conductive fabrics. Such materials includestainless steel, transparent conductive film, rubber, copper, silver,tungsten, aluminum, zinc, iron, platinum, tin, lead, titanium, carbonsteel. Both the electrodes on the wrist and the exterior electrodes canbe made of a variety of conductive materials, however, flexible andforgiving materials provide adaptability for patients of varying wristsize such that the electrodes still make consistent, firm contact withthe patient's skin.

In other embodiments, the handheld device described above can integratewith a ‘patch’ that directly adheres to a portion of a patient's body,or a ‘necklace’ that drapes around the patient's neck. The patch wouldbe similar in form to the necklace's base, although it may take on othershapes and form factors. It would include most or all of the samesensors (e.g. sensors for measuring ECG, TBI, and PPG waveforms) andcomputing systems (e.g. microprocessors operating algorithms forprocessing these waveforms to determine parameters such as HR, HRV, RR,BP, SpO2, TEMP, CO, SV, fluids) as the base of the necklace. Howeverunlike the system described above, the battery to power the patch wouldbe located in or proximal to the base, as opposed to the strands in thecase of the necklace. Also, in embodiments, the patch would include amechanism such as a button or tab functioning as an on/off switch.Alternatively, the patch would power on when sensors therein (e.g. ECGor temperature sensors) detect that it is attached to a patient.

In typical embodiments, the patch includes a reusable electronics module(shaped, e.g., like the base of the necklace) that snaps into adisposable component that includes electrodes similar to those describedabove. The patch may also include openings for optical and temperaturesensors as described above. In embodiments, for example, the disposablecomponent can be a single disposable component that receives thereusable electronics module. In other embodiments, the reusableelectronics module can include a reusable electrode (made, e.g., from aconductive fabric or elastomer), and the disposable component can be asimple adhesive component that adheres the reusable electrode to thepatient.

In preferred embodiments the patch is worn on the chest, and thusincludes both rigid and flexible circuitry, as described above. In otherembodiments, the patch only includes rigid circuitry and is designed tofit on other portions of the patient's body that is more flat (e.g. theshoulder).

In embodiments, for example, the system described above can calibratethe patch or necklace for future use. For example, the handheld devicecan determine a patient-specific relationship between transit time andblood pressure, along with initial values of SYS, DIA, and MAP.Collectively these parameters represent a cuff-based calibration forblood pressure, which can be used by the patch or necklace for cufflessmeasurements of blood pressure. In other embodiments, the handhelddevice can measure a full-body impedance measurement and weight. Theseparameters can be wirelessly transmitted to the necklace or patch, wherethey are used with their impedance measurement to estimate full-bodyimpedance (e.g. during a dialysis session). Additionally, during thedialysis session, the necklace or patch can use the values of full-bodyimpedance and weight to estimate a progression towards the patient's dryweight.

These and other embodiments of the invention are deemed to be within thescope of the following claims.

The invention claimed is:
 1. A biometric sensor configured to measure aphysiological parameter from a patient, comprising: an arm-receivingportion comprising an opening configured to receive a distal portion ofthe patient's arm, an inflatable cuff comprising a pair of inflatablebladders that oppose each other across the opening and are configured toengage the distal portion of the patient's arm, and a first electrodeconfigured and arranged to contact the distal portion of the patient'sarm when it is inserted in the opening; a body-contacting portionconnected to the arm-receiving portion and comprising a second electrodeconfigured and arranged to contact a second body location that is one ofthe patient's torso, legs, opposing arm, and neck when thebody-contacting portion contacts the second body location while thedistal portion of the patient's arm is inserted in the opening; ananalog system configured to receive biometric signals from the firstelectrode and the second electrode and to process them to generate ananalog physiological waveform; and a digital system configured todigitize the analog physiological waveform and to process it withcomputer code to determine the physiological parameter.
 2. The biometricsensor of claim 1, wherein the analog system comprises a differentialamplifier configured to amplify a difference between the biometricsignals received from the first and second electrodes to generate ananalog physiological waveform.
 3. The biometric sensor of claim 2,wherein the analog physiological waveform comprises heartbeat-inducedpulsations.
 4. The biometric sensor of claim 3, wherein the analogphysiological waveform is an electrocardiogram (ECG) waveform.
 5. Thebiometric sensor of claim 4, wherein the ECG waveform comprises a set ofheartbeat-induced QRS complexes, and the computer code is configured tocalculate a time difference between the QRS complexes to determine thepatient's heart rate.
 6. The biometric sensor of claim 1, wherein thearm-receiving portion comprises first and second spaced-apart wallportions that form the opening, which wall portions are arranged so asto be located on opposite sides of the patient's arm when it is insertedin the opening.
 7. The biometric sensor of claim 6, wherein the firstand second wall portions extend from the body-contacting portion.
 8. Thebiometric sensor of claim 6, wherein the first electrode is disposed onan inner surface of one of the first and second wall portions.
 9. Thebiometric sensor of claim 1, wherein the arm-receiving portion comprisesan annular ring component that forms the opening.
 10. The biometricsensor of claim 9, wherein the first electrode is disposed on an innersurface of the annular ring component.
 11. The biometric sensor of claim1, wherein the cuff is formed from an elastomeric material.
 12. Thebiometric sensor of claim 1, wherein the cuff is formed from aninelastic material.
 13. The biometric sensor of claim 1, wherein thecuff is configured to be wrapped around the distal portion of thepatient's arm and secured by means of a closure member.
 14. Thebiometric sensor of claim 1, wherein the first and second electrodeseach comprise a conductive material.
 15. The biometric sensor of claim14, wherein the conductive material is one of a conductive fabric, ametal component, a conductive foam, a conductive polymeric material, anda hydrogel material.
 16. The biometric sensor of claim 1, wherein thefirst electrode is disposed on top of an inflatable bladder.
 17. Thebiometric sensor of claim 16, wherein the sensor further comprises amicroprocessor-controlled pneumatic inflation system configured andarranged to control inflation and deflation of the inflatable bladder.18. The biometric sensor of claim 16, wherein the first electrode isformed from elastomeric fabric that stretches and contracts with theinflatable bladder as the bladder is inflated and deflated.
 19. Thebiometric sensor of claim 1, further comprising a circuit board disposedwithin one of the arm-receiving portion or the body-contacting portion.20. The biometric sensor of claim 19, wherein the analog and digitalsystems are disposed on the circuit board and the digital systemincludes a microprocessor that is programmed with said computer code toprocess the analog physiological waveform to determine the physiologicalparameter.
 21. The biometric sensor of claim 20, wherein the first andsecond electrodes are in electrical, signal-conducting contact with theanalog system.
 22. A biometric sensor configured to measure aphysiological parameter from a patient, comprising: an arm-receivingportion comprising an opening configured to receive a distal portion ofthe patient's arm, an inflatable cuff comprising a pair of inflatablebladders that oppose each other across the opening and are configured toengage the distal portion of the patient's arm, and a first electrodeconfigured and arranged to contact the distal portion of the patient'sarm when it is inserted in the opening, wherein the first electrode isformed from a conductive, elastomeric material disposed over a surfaceof one of the inflatable bladders that faces the opening; abody-contacting portion, connected to the arm-receiving portion, andcomprising a second electrode configured and arranged to contact asecond body location that is one of the patient's torso, legs, opposingarm, and neck when the body-contacting portion contacts the second bodylocation while the distal portion of the patient's arm is inserted inthe opening; an analog system configured to receive biometric signalsfrom the first electrode and the second electrode and to process them togenerate an analog physiological waveform; and a digital systemconfigured to digitize the analog physiological waveform and to processit with computer code to determine the physiological parameter.